Precision measurement systems have been developed for the measurement of current pulses having amplitudes of no more than a few pico-amperes and durations of one hundred milliseconds or less as those pulses occur in the individual ionic channels of biological membranes such as muscle fibers. In one effective system of this kind, a glass pipette containing an internal electrode is pressed against the biological membrane to form a seal having a high electrical resistance. A current pulse occurring in the portion of the membrane engaged by the pipette flows, for the most part, into the internal electrode of the pipette as described in Pflugers Archiv/European Journal of Physiology 375, page 219-228 (1978); a copy of that publication is submitted with this application. A reference potential, which controls the potential in the pipette and at the membrane, may be applied so that they will be held at ground potential or at any other desired constant potential. The current in the pipette electrode is supplied to a current-to-voltage converter circuit and then to an output amplifier connected to an oscilloscope or oscillograph.
In precision measurement systems of this kind, the principal problem that must be overcome is background noise. Such background noise, which is difficult to avoid or eliminate, severely affects the current resolution that may be achieved within a desired band width.